Consumption of refined sugars in the form of sucrose and high-fructose corn syrup is very high in the U.S. and in the Western world. While the public health implications of this phenomenon have been studied extensively, the recent discovery of fructose-3-phosphate (F3P) in human erythrocytes suggests that fructose metabolism in man should be examined further, with a particular emphasis on this novel metabolic pathway. Such a study is needed because preliminary data suggest that erythrocytic F3P in man is produced primarily from dietary fructose and that F3P is an important systemic source of a potent reactive ketoaldehyde 3- deoxyglucosone (3DG). This compound is considered to be a key this a key intermediate in the process of non-enzymatic glycation of proteins which appears to be involved in the etiology of diabetic complications. Published evidence suggests that this toxic compound is produced in-vivo in animals and man and is detoxified by reduction to 3-deoxyfructose (3DF). This proposal seeks to investigate the details of synthesis of fructose-3- phosphate in human erythrocytes ex vivo and in vivo with a particular emphasis on understanding the detoxification mechanisms and their possible impairment in pathological conditions such as hyperglycemia.